<p>This study focuses on the rural self-built house with a frame bottom floor and three masonry upper floors. This model is a prototype of traditional self-built houses still prevalent in Chinese rural areas, which pose a significant risk of damage during earthquakes due to the structural weaknesses of the first and second floors. Despite its vulnerability, many residents continue to construct such houses due to their comfort and convenience. By subjecting the structure to seven seismic records, we analyze the seismic responses of the first floor frame structure, first floor shear wall structure, first floor seismic isolation structure, and second floor seismic isolation structure. A comparative assessment of the seismic performance of these four structures under earthquake conditions is conducted. The study indicates that after an earthquake, the primary damage to the building structure occurs in the first floor and the top node. The first floor shear wall structure reduces seismic actions to some extent. The seismic isolation story effectively prolongs the structural period and prevents resonance with the site’s predominant period. When first floor seismic isolation structure is adopted, the acceleration, inter-story shear, inter-story drift and base shear response of the structure are reduced to 19.9%, 20.2%, 30.9%, and 26.0% of the first floor frame structure, and the effect is very significant. Second floor seismic isolation structure is more effective than first floor shear wall structure, and first floor seismic isolation structure surpasses both second floor seismic isolation structure and first floor shear wall structure. The use of first floor seismic isolation structure, second floor seismic isolation structure, and first floor shear wall structure enhances structural performance and effectively mitigates demand to reinforced concrete and masonry elements of traditional earthquake-resistant structures during seismic events.</p>